# Developmental Effects of Manganese Exposure in Rural Adolescents: The CARES Cohort Comes of Age

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2020 · $505,975

## Abstract

Manganese (Mn) plays an essential role in normal growth and development; however,
overexposure to Mn can result in neurotoxicity. This dual role of Mn as essential mineral and
neurotoxicant appears as a biphasic dose-response curve for neurodevelopmental health
outcomes in children. Children may be particularly susceptible to the neurotoxic effects of
ambient Mn exposure, as their brains are undergoing a dynamic process of growth,
differentiation, pathway direction, and apoptosis, all of which can be influenced by
environmental factors. Recent developments in magnetic resonance imaging (MRI) and
spectroscopy (MRS) can provide novel, quantitative information about the effects of Mn on brain
anatomy and physiology; yet these imaging methods have never been applied to an adolescent
population exposed to chronic ambient Mn. Given the role of Mn as both nutrient and
neurotoxicant, we anticipate that biomarkers of Mn exposure will exhibit a biphasic dose-
response association with adolescent neurobehavior, neuromotor function, brain
anatomy and physiology, and hypothesize that both low (1st quartile) and high (4th
quartile) levels of exposure will be significantly associated with deficits in these
domains. This overarching hypothesis will be addressed through two specific aims.
Specific Aim 1: Evaluate neurodevelopment with historic and current biomarkers of Mn in a
cohort of rural adolescents in order to evaluate the impact of Mn from essential to excess on
executive function, attention and reaction time, cognition, achievement, behavior, and
neuromotor status. Specific Aim 2: Conduct a sub-study of adolescents based on previously
determined Mn biomarkers using quantitative MRI/S in order to evaluate the effects of Mn
exposure from essential to excess on neuroanatomy, metabolism, organization, function and
connectivity. Neuroimaging outcomes (volume, metabolite concentrations, metrics for diffusion
tensor, functional activation, and network connectivity) will be compared with historic and
current biomarkers of Mn. This well-characterized longitudinal cohort study of adolescents will
advance our understanding of the impact of Mn on neurodevelopment, and brain anatomy and
physiology using innovative MRI methodologies. These patterns may be useful in defining the
lines of essential benefit and neurotoxicological harm from Mn. The findings from this study will
have regional, national and global implications for advancement of neuroscience and will be
used to inform policy related to Mn in gasoline and ambient air standards. This proposal
leverages the only cohort available in the United States that can directly address these aims.

## Key facts

- **NIH application ID:** 9767766
- **Project number:** 5R01ES026446-05
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Kim M Cecil
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $505,975
- **Award type:** 5
- **Project period:** 2016-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9767766

## Citation

> US National Institutes of Health, RePORTER application 9767766, Developmental Effects of Manganese Exposure in Rural Adolescents: The CARES Cohort Comes of Age (5R01ES026446-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9767766. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*